Tetracyclic Thioxanthene Derivatives: Studies on Fluorescence and Antitumor Activity

• Main Authors: Fernando Durães, Patrícia M. A. Silva, Pedro Novais, Isabel Amorim, Luís Gales, Cátia I. C. Esteves, Samuel Guieu, Hassan Bousbaa, Madalena Pinto, Emília Sousa
• Format: Article
• Language: English
• Published: MDPI AG 2021-05-01
• Series: Molecules
• Subjects: thioxanthenes; theranostic; antitumor activity; photophysics
• Online Access: https://www.mdpi.com/1420-3049/26/11/3315

Thioxanthones are bioisosteres of the naturally occurring xanthones. They have been described for multiple activities, including antitumor. As such, the synthesis of a library of thioxanthones was pursued, but unexpectedly, four tetracyclic thioxanthenes with a quinazoline–chromene scaffold were obtained. These compounds were studied for their human tumor cell growth inhibition activity, in the cell lines A375-C5, MCF-7 and NCI-H460. Photophysical studies were also performed. Two of the compounds displayed GI₅₀values below 10 µM for the three tested cell lines, and structure–activity relationship studies were established. Three compounds presented similar wavelengths of absorption and emission, characteristic of dyes with a push-pull character. The structures of two compounds were elucidated by X-ray crystallography. Two tetracyclic thioxanthenes emerged as hit compounds. One of the two compounds accumulated intracellularly as a bright fluorescent dye in the green channel, as analyzed by both fluorescence microscopy and flow cytometry, making it a promising theranostic cancer drug candidate.